Directed differentiation of postnatal hippocampal neural stem cells generates nuclear receptor related-1 protein- and tyrosine hydroxylase-expressing cells

Abstract

Parkinson's disease (PD) is a severe neurodegenerative disorder. Although the detailed underlying molecular mechanism remains to be elucidated, the major pathological feature of PD is the loss of dopaminergic (DA) neurons of the substantia nigra. The use of donor stem cells to replace DA neurons may be a key breakthrough in the treatment of PD. In the present study, the growth kinetics of hippocampal neural stem cells (Hip-NSCs) isolated from postnatal mice and cultured in vitro were observed, specifically the generation of cells expressing DA neuronal markers nuclear receptor related-1 protein (Nurr1) and tyrosine hydroxylase (TH). It was revealed that Hip-NSCs differentiated primarily into astrocytes when cultured in serum-containing medium. However, in low serum conditions, the number of βIII tubulin-positive neurons increased markedly. The proportion of Nurr1-positive cells and TH-positive neurons, significantly increased with increasing duration of directed differentiation of Hip-NSCs (P=0.0187 and 0.0254, respectively). The results of the present study reveal that Hip-NSCs may be induced to differentiate in vitro into neurons expressing Nurr1 and TH, known to be critical regulators of DA neuronal fate. Additionally, their expression may be necessary to facilitate neuronal maturation in vitro. These data suggest that Hip-NSCs may serve as a source of DA neurons for cell therapy in patients diagnosed with PD.

Effect of Wnt1 and Wnt5a on the development of dopaminergic neurons, and toxicity induced by combined exposure to paraquat and maneb during gestation and lactation

“…Previous studies have demonstrated that Nurr1 directly regulates the promoter of TH gene (37). Upon activation, Nurr1 translocates to the nucleus, where it binds to the promoter region and activates the transcription of TH (38).…”

Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson’s disease model

“…In recent years, research on NSCs' direct differentiation toward specific subtypes of neurons is the hotspot. A bunch of studies reported the generation of dopaminergic neurons from NSCs (Ding et al 2016;Lee et al 2016a, b). Due to the fact that degradation of dopaminergic neurons plays key roles in the pathology of Parkinson's disease (PD), development of stem cell-based therapy is one of the most promising way in the treatment of PD (Zhu et al 2016).…”

Abnormal Development of Neural Stem Cell Niche in the Dentate Gyrus of Menkes Disease

“…To induce neuronal differentiation, the medium was replaced with serum-free Neurobasal medium (Gibco BRL, Gaithersburg, MD) supplemented with B27 (Gibco BRL, Gaithersburg, MD), Glutamax (Gibco-Invitrogen, Grand Island, NY), and 200 nM cytosine arabinoside (Sigma-Aldrich, St. Louis, MO). For copper accumulation assay, copper (1 μg/ml) was added into the culture medium along with copper chloride (1 μg/μL, Sigma-Aldrich, St. Louis, MO) as previously described ( 19 , 20 ).…”